Unveiling the neuroprotective potential of vortioxetine on inflammation in the cuprizone-induced demyelination model.

Abstract

Multiple sclerosis (MS) is a chronic demyelinating and autoimmune disorder of the central nervous system characterized by immune-mediated damage to oligodendrocytes and myelin sheaths. To model demyelination, we used the cuprizone paradigm in male C57BL/6 mice, in which copper chelation induces selective oligodendrocyte toxicity and glial activation. This model produces behavioral and motor disturbances, including cognitive impairment, anxiety-like behavior, and reduced motor performance. Vortioxetine, a multimodal serotonergic antidepressant, acts through inhibition of the serotonin transporter and modulation of multiple neurotransmitter systems. Emerging evidence suggests that vortioxetine may exert neuroprotective and anti-inflammatory effects, making it a potential candidate for neuroinflammatory conditions. In this study, male C57BL/6 mice were administered cuprizone for five weeks to induce demyelination, and vortioxetine was delivered intraperitoneally to evaluate its effects on neuroinflammation, anxiety-like behavior, spatial memory, and object recognition. Cytokine levels (TNF-α, IL-1β) were quantified using ELISA, and behavioral performance was assessed using the open-field, elevated plus maze, Y-maze, and object location recognition tests. Vortioxetine significantly attenuated cuprizone-induced increases in proinflammatory cytokines in cortical tissue and improved anxiety-like behavior and cognitive performance without altering general locomotor activity. These findings demonstrate that vortioxetine exerts anti-inflammatory and neurobehavioral effects in the cuprizone-induced demyelination model. The observed modulation of cytokine levels and behavioral outcomes suggests potential relevance to neuroinflammatory conditions such as MS; however, further studies are required to establish its therapeutic efficacy in clinical settings.